Impaired therapeutic efficacy of sleep-deprived bone marrow mesenchymal stem cells in the cerebellum of mouse cuprizone model of multiple sclerosis: stereological and motor behavioral evidence.

Abstract

Multiple sclerosis (MS) leads to histological changes, which in turn result in functional deficits. Studies have reported that bone marrow mesenchymal stem cells (BMSCs) have therapeutic benefits in MS. In addition, sleep deprivation affects therapeutic potential of BMSCs. This research aimed to evaluate the effects of BMSCs compared to sleep-deprived BMSCs (SD-BMSCs) on the motor behavior and histological recovery in MS. The mice were divided into four groups receiving cuprizone for five weeks, with or without intranasal administration of cells (BMSCs or SD-BMSCs) after five weeks. After a two-week recovery period, balance beam and pole tests were performed to assess motor performance, followed by estimation of histological parameters using stereological methods. Mice that received BMSCs scored significantly better than the SD-BMSC group in balance beam and pole tests (P&#x2009;<&#x2009;0.05). The total cerebellar volume, cortex, and white matter volumes, as well as the total number of Purkinje cells in mice that received BMSCs, were significantly higher compared to those in the SD-BMSC group (P&#x2009;<&#x2009;0.05). Intranasal administration of BMSCs leads to significantly improved motor behavior and histological regeneration of the cerebellum, including cortex and white matter as well as Purkinje cells compared to SD-BMSCs in a cuprizone model of multiple sclerosis.